title: Expression of PPAR γ in intestinal epithelial cells is dispensable for the prevention of colitis by dietary abscisic acid.
abstract: OBJECTIVE
  Dietary abscisic acid (ABA) has shown efficacy in ameliorating experimental IBD in mice through mechanisms requiring expression of peroxisome proliferator activated-receptor γ (PPAR γ) in immune cells. The goal of this study was to determine whether PPAR γ expression in colonic epithelial cells is required for the anti-inflammatory actions of ABA.
  
  
  METHODS
  Conditional knockout mice expressing a transgenic recombinase in intestinal epithelial cells under the control of a villin promoter (PPAR γ flfl; Villin Cre+ or VC+) with defective expression of PPAR γ in intestinal cells (IEC) and PPAR γ-expressing wild type (PPAR γ flfl; Villin Cre- or VC-) mice in a C57BL/6 background were fed diets with and without ABA (0.1 g/kg) for 35 days and challenged with 2.5% dextran sodium sulfate (DSS) in the drinking water for 7 days. Clinical disease severity was assessed daily and colonic lesions on day 7 through macroscopic and histopathological examination. Immune cell phenotypes were examined systemically and at the mesenteric lymph nodes (MLN). Epithelial gene expression was assayed in the colon.
  
  
  RESULTS
  Dietary ABA-supplementation prevented colitis, reduced disease severity, improved colonic histopathology, and upregulated epithelial lanthionine synthetase C-like protein 2 (LANCL2) expression in VC+ mice. Dietary ABA significantly increased the percentages of MLN CD4+IL-10+ T cells, and blood CD4+CD25+FoxP3+ T cells and CD8+IL-10+ T cells.
  
  
  CONCLUSIONS
  Expression of PPAR γ in IECs was not required for the anti-inflammatory efficacy of ABA in IBD. LANCL2 in IECs and T cell-derived IL-10 may be implicated in the mechanism underlying ABA's immune modulatory activity in IBD.
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Center for Modeling Immunity to Enteric Pathogens, Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, 24060, United States of America.
authors.forename: Raquel
authors.initials: R
authors.lastname: Hontecillas
authors.forename: Josep
authors.initials: J
authors.lastname: Bassaganya-Riera
keywords: Crohn’s disease; Inflammatory bowel disease; PPARγ; abscisic acid; intestinal epithelial cells; lanthionine synthetase C-like protein 2; ulcerative colitis